383TiPBintrafusp alfa (M7824) and eribulin mesylate in treating patients with metastatic triple negative breast cancer (TNBC)(NCT03579472)

AbstractBackgroundTNBC is an aggressive subtype of metastatic breast cancer. Eribulin has been shown to have activity in metastatic TNBC and has enhanced efficacy if TGF- β is downregulated. Additionally, down-regulating TGF-β in the tumor microenvironment may decrease tumor growth and increase responsiveness to checkpoint blockade. Bintrafusp alfa* (M7824) is an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-β RII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Therefore the combination of eribulin with bintrafusp alfa is being tested in this phase I trial to evaluate safety and efficacy for patients with metastatic TNBC.Trial designThis is an open-label, single arm phase Ib study in patients with metastatic TNBC. The primary objective is to evaluate the recommended phase-2 dosing of eribulin and bintrafusp. Patients undergo core tissue biopsy and blood work at enrollment. Patients will then receive study drug (bintrafusp alfa) and eribulin with tumor assessments at 6 and 12 weeks. Patients will be treated in a cohort size of 4 with an expansion of up to 20 patients. Bayesian optimal interval (BOIN) design will be employed to identify the RP2D of eribulin by conducting dose de-escalations based on dose-limiting toxicity. Patients undergo repeat core tissue biopsy after 12 weeks of therapy and will continue on study drug until progression of disease or a sustained CR for one year. Eligibility: ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research